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  • Björk, KarlKarolinska Institutet (author)

β-Arrestin 2 knockout mice exhibit sensitized dopamine release and increased reward in response to a low dose of alcohol

  • Article/chapterEnglish2013

Publisher, publication year, extent ...

  • 2013-06-19
  • Springer,2013
  • printrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:liu-94653
  • https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-94653URI
  • https://doi.org/10.1007/s00213-013-3166-xDOI
  • http://kipublications.ki.se/Default.aspx?queryparsed=id:127776655URI

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  • Language:English
  • Summary in:English

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  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • RationaleThe rewarding effects of alcohol have been attributed to interactions between opioid and dopaminergic system within the mesolimbic reward pathway. We have previously shown that ablation of β-arrestin 2 (Arrb2), a crucial regulator of μ-opioid receptor function, attenuates alcohol-induced hyperlocomotion and c-fos activation in the nucleus accumbens.ObjectivesHere, we further investigated the role of Arrb2 in modulating alcohol-induced dopamine (DA) release and conditioned place preference (CPP). We also assessed the functional importance of Arrb2 for μ-opioid receptor surface expression and signaling following an acute alcohol challenge.MethodsAlcohol-evoked (0.375, 0.75, and 1.5 g/kg intraperitoneally) DA release was measured by in vivo microdialysis in the shell of nucleus accumbens. Reward was assessed by the CPP paradigm. Receptor function was assessed by μ-receptor binding and [35S]GTP-γ-S autoradiography.ResultsIn Arrb2 knockout mice accumbal DA levels reach maximum response at a lower dose compared to wild-type (wt) animals. In line with these results, Arrb2 knockout mice display increased CPP for alcohol as compared to wt mice. Finally, Arrb2 mutant mice display increased μ-opioid receptor signaling in the ventral and dorsal striatum and amygdala in response to a low dose of alcohol, indicating impaired desensitization mechanisms in these mice.ConclusionsOur results show that Arrb2 modulates the response to low doses of alcohol on various levels including μ-opioid receptor signaling, DA release, and reward. They also reveal a clear dissociation between the effects of Arrb2 on psychomotor and reward behaviors.

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Added entries (persons, corporate bodies, meetings, titles ...)

  • Tronci, ValeriaPsychobiology Section, NIDA, National Institutes of Health, Baltimore, MD, USA (author)
  • Thorsell, AnnikaLinköpings universitet,Avdelningen för neuro- och inflammationsvetenskap,Medicinska fakulteten,Centrum för social och affektiv neurovetenskap (CSAN)(Swepub:liu)annth96 (author)
  • Tanda, GianluigiPsychobiology Section, NIDA, National Institutes of Health, Baltimore, MD, USA (author)
  • Hirth, NatalieUniversity of Heidelberg, Mannheim, Germany (author)
  • Heilig, MarkusLaboratory of Clinical and Translational Studies, NIAAA, National Institutes of Health, Bethesda, MD, USA(Swepub:liu)marhe41 (author)
  • Hansson, Anita C.Laboratory of Clinical and Translational Studies, NIAAA, National Institutes of Health, Bethesda, MD, USA (author)
  • Sommer, Wolfgang HLaboratory of Clinical and Translational Studies, NIAAA, National Institutes of Health, Bethesda, MD, USA (author)
  • Karolinska InstitutetPsychobiology Section, NIDA, National Institutes of Health, Baltimore, MD, USA (creator_code:org_t)

Related titles

  • In:Psychopharmacology: Springer230:3, s. 439-4490033-31581432-2072

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